Cytochrome P450 2D6 polymorphisms and predicted opioid metabolism in African American children with sickle cell disease.
J Pediatr Hematol Oncol
; 35(7): e301-5, 2013 Oct.
Article
em En
| MEDLINE
| ID: mdl-23619115
ABSTRACT
The opioid medications codeine and hydrocodone, commonly prescribed in sickle cell disease (SCD), require metabolic conversion by cytochrome P450 2D6 (CYP2D6) to morphine and hydromorphone, respectively, to exert their analgesic effects. The CYP2D6 gene is highly polymorphic, with variant alleles that result in decreased, absent, or ultrarapid enzyme activity. Seventy-five children with SCD were tested for CYP2D6 polymorphisms, and metabolic phenotypes were inferred from the genotypes. The most common variant alleles were CYP2D6*2 (normal activity, 28.7%), CYP2D6*17 (reduced activity, 17.3%), CYP2D6*5 (gene deletion, 8.7%), and CYP2D6*4 (absent function, 8.0%). Normal/extensive metabolizer genotypes were found in 28/75 (37.5%), intermediate metabolism in 33/75 (44.0%), poor metabolism in 4/75 (5.3%), ultrarapid metabolism in 3/75 (4.0%), indeterminate in 6/75 (8.0%). Allele frequencies did not vary significantly among different hemoglobin genotypes. Identification of variant CYP2D6 genotypes may identify individuals with altered metabolism and therefore altered analgesic response to codeine and hydrocodone, thus providing a personalized medicine approach to treatment of pain in SCD. Further pharmacokinetic and pharmacodynamic studies are needed to define the relationship of CYP2D6 and other gene polymorphisms to individual opioid effect in SCD.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
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Negro ou Afro-Americano
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Citocromo P-450 CYP2D6
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Analgésicos Opioides
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Anemia Falciforme
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Child
/
Humans
Idioma:
En
Revista:
J Pediatr Hematol Oncol
Assunto da revista:
HEMATOLOGIA
/
NEOPLASIAS
/
PEDIATRIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Gabão